Since the complete sequencing of the human genome by the U.S. Department of Energy and the NIH in 2003, extensive research has been focused on understanding human genetics and how it impacts our health. The ability to sequence complete genomes and the vast amount of existing sequence data has led to widespread advancements in all areas of health care, from preventative treatment to early detection to optimization in therapy. Knowledge of an individual's genotype can maximize the probability of successful treatment by reducing trial-and-error prescribing, increasing patient compliance with therapy, and reducing adverse drug reactions. Today, genetic testing plays a role in the surveillance and treatment of a number of disorders, including various types of cancer, coagulation disorders, and cardiac health. Personalized genomics can also revolutionize medicine by improving the selection of targets for drug discovery, reducing the time, cost, and failure rate of clinical trials, and avoiding the withdrawal of marketed drugs. In addition to DNA sequence, knowledge of an individual's epigenetic makeup and DNA damage profile can assist in the diagnosis and treatment of disease, and has been implicated in important biological processes such as aging and neurological diseases such as Alzheimer's and Parkinson's disease.
Despite progress, the new era of personalized health for every individual is impeded by the high costs of genome sequencing and DNA analysis. Without large reductions in sequencing costs, genome sequencing cannot be used routinely for individual health care. This need to reduce cost while maintaining sequencing quality has sparked the $1100 genome program by the NHGRI, which has catalyzed many innovative approaches to DNA sequencing (see e.g. Schloss et al. Nature Biotechnology 2008, 26 (10), 1113-1115). The current invention provides for improved sequencing.